Description of Druglike Properties of Safranal and Its Chemistry behind Low Oral Exposure

Abstract

Safranal, a plant secondary metabolite isolated from saffron, has been reported for several promising pharmacological properties toward the management of Alzheimer's disease. In the present study, we observe and report for the first time about several druglike attributes of safranal, such as adherence to Lipinski's rule of five; optimum lipophilicity; high permeability; low blood-to-plasma ratio; less to moderate propensity to interact with P-glycoprotein (P-gp) or breast cancer-resistant protein (BCRP) transporters; and high plasma protein binding as common to most of the marketed drugs using in vitro and ex vivo models. In spite of the above attributes, in vivo oral absorption was found to be very poor, which is linked to the structural integrity of safranal in simulated gastric fluid, simulated intestinal fluid, plasma, and liver microsomes. Moreover, the presence of unsaturated aldehyde moiety in safranal remains in equilibrium with its hydroxylated acetal form. Further research work is required to find out the stable oral absorbable form of safranal by derivatization of its aldehyde group without losing its potency.

Pharmacokinetic Assessment of Rottlerin from Mallotus philippensis Using a Highly Sensitive Liquid Chromatography–Tandem Mass Spectrometry-Based Bioanalytical Method

“…The concentration of rottlerin was measured by this new LC–MS/MS method, whereas standards for specific experiments were measured by our in-house HPLC–UV or LC–MS/MS methods. We performed the above-mentioned studies using our earlier reported protocols − and detailed methodologies for each parameter are described in the Supporting Information.…”

Mineral Content and Volatile Profiling of Prunus avium L. (Sweet Cherry) By-Products from Fundão Region (Portugal)

“…Safranal (26) is a plant secondary metabolite isolated from saffron and was found in an aqueous infusion of P. avium leaves ( Table 3 ). Promising pharmacological properties have been described for this compound, namely neuroprotective and anti-inflammatory activities [ 40 , 41 ]. No data could be found in the literature on the presence of safranal in P. avium fruits and their by-products.…”

TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells

“…Yoshida et al observed that some monoterpenoids from Zanthoxyli fructus were inhibitors of ABCB1 protein [ 37 ] but they did not interfere with transport activity of ABCC2 and ABCBG2 [ 38 ]. Safranal was also found to affect ABCB1 and ABCG2 transporters, increasing their ATP-ase activity [ 39 ]. Potent MDR modulators have been identified among more complex terpenes such as jathropane [ 40 ] and lathyrane diterpenes [ 24 , 41 ].…”